Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignant cancers with high incidence and mortality. Current reliable effective diagnostic and prognostic biomarkers are very limited in clinic. Emerging evidence indicates that dysregulated expression of the long non-coding RNAs (lncRNAs) was examined in various types of cancer including ESCC. ESCC associated lncRNA _1 (ESCCAL_1) was first time identified to be increased expression in ESCC, and therefore named by our research team. However, its potential function in the progression of ESCC remains unclear. In this study, we investigated the effect of ESCCAL_1 knockdown on ESCC tumorigenicity using a xenograft mouse model and explored the underlying molecular mechanism. Here we showed that ESCCAL_1 knockdown significantly inhibited EC9706 cell growth in nude mice. Interestingly, we also found that reduced expression of ESCCAL_1 resulted in distinct alterations of relative phosphorylation level of kinases (p-p38α, p-JNK, p-FAK and p-Src), and significant changes of the expression level of apoptosis-related proteins (p53, BAX, Bcl-2 and Caspase-3). In summary, our results suggest that lncRNA ESCCAL_1 is a potential diagnostic and prognostic target of ESCC.